The complement receptor of B lymphocytes is expressed evidently late during development of the B cell lineage. Functional studies in vivo and in vitro have shown that both CR+ ("late") and CR- ("early") B lymohocytes are capable of producing antibody. The central question of this proposal is whether CR- populations can differentiate to plaque forming cells (PFC) without passing through a CR+ differentiative state, or whether the CR+ state is an obligatory intermediary. Since the in vitro immune response requires the complex interaction of several cell types (which may obscure the tissue of B cell differentiation), we propose to use LPS for polyclonal activation of B cells in the absence of accessory cells. We will determine the kinetics of initiation of Ig synthesis in isolated Cr- and CR+ B cell populations. Starting with CR-B cells, we will induce CR by culturing with LPS, and test whether after removal of CR+ cells Ig synthesis is delayed. Based on our observation that factors derived from helper T cells induce differentiation in early B cells, we will investigate the significance of an intact T cell compartment for the maturation of B cells. We will analyze the state of B cell maturity in T cell deficient mice and attempt to reconstitute the T cell compartment if defects in the B cell lineage become apparent.